The applicants proposed to design and fabricate a transurethral acoustic waveguide system for the ablation of abnormal human prostatic tissue involved with benign prostatic hypertrophy (BPH) and prostate cancer. The general approach would be to employ an acoustic waveguide and a transurethral approach to apply high-intensity focused ultrasound (HIFU) to the prostate gland. The applicants proposed to begin by developing a prototype waveguide system using a large external transducer to create high levels of sonic energy which would be transmitted to the prostate gland by the waveguide, and brought to a sufficiently sharp focus within the prostate to cause thermal ablation. The waveguide system would potentially be capable of moving the treating focal spot along 3 degrees of freedom so as to translate the ultrasonic energy through the regions of the prostate to be ablated in a controlled manner. The applicants would evaluate the waveguide system in vitro by acoustic field mapping using a Schlieren photographic process, and in studies of phantoms and excised tissues, and would determine an optimal treatment protocol in terms of the electrical power applied to the system, the most effective techniques for moving the focal spot of the waveguide, and the best way in which to cool and protect sensitive normal structures near the prostate using a circulating water bath. Subsequent evaluations in dogs would be performed with the insonification protocol determined to be most optimal from the in vitro work, in order to evaluate the ability of the device to produce controlled prostatic ablation in vivo, and to assess the degree of damage to adjacent periprostatic tissues. All phantom and animal studies would be performed with new MR thermal mapping techniques for monitoring tissue heating. These techniques would include rapid T1-weighted and phase-sensitive MR imaging optimized for this application. Upon completion of this work, the applicants expect to have developed and tested an acoustic waveguide system, with ultrasonic delivery guided by thermal mapping with MRI, that has the potential for highly effective and minimally invasive treatment of BPH and local control of prostate cancer.